Aging_Primates - BREVIA Cellular Senescence in Aging...

Cellular Senescence inAging PrimatesUtz Herbig,1Mark Ferreira,1Laura Condel,2Dee Carey,2John M. Sedivy1*The aging of organisms is characterizedby a gradual functional decline of allorgansystems.Mammaliansomaticcells in culture display a limited proliferativelife span, at the end of which they undergo anirreversible cell cycle arrest known as repli-cative senescence. Whether cellular senescencecontributes to organismal aging has been con-troversial. To reinvestigate this question, weassayed the skin of aging baboons for telo-mere dysfunction, a recently discovered bio-marker of cellular senescence (1).Like humans, baboons have a relativelylong life span and show age-dependent telo-mere shortening (2). Baboon skin fibroblastsundergo replicative senescence upon serial pas-sage in culture, with characteristics identical tothose of human fibroblasts. Senescent baboonfibroblasts display DNA damage foci that con-tain phosphorylated histone H2AX (g-H2AX),activated ataxia-telangiectasia mutated (ATM)kinase ATM(Ser1981), and p53 binding protein(53BP1), and they express activated p53(Ser15)and elevated levels of p21CIP1. More than 80%of senescent baboon fibroblasts in vitro displaytelomere dysfunction–induced foci (TIFs), asdetermined by the colocalization ofg-H2AXwith telomeres.Full-thickness skin biopsies were obtainedfrom 30 baboons (15 male and 15 female), rang-ing in age from 5 to 30 years, that were born andraised at the Southwest Regional Primate Centerunder controlled conditions. The tissue was har-vested from the medial aspect of the forearm, asurface that is relatively protected from radiationand injury. The number of dermal fibroblast nu-

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